| Project/Area Number |
18H02682
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Kume Tsutomu 熊本大学, 生命資源研究・支援センター, 客員教授 (60786474)
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| Co-Investigator(Kenkyū-buntansha) |
南 敬 熊本大学, 生命資源研究・支援センター, 教授 (00345141)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
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| Keywords | リンパ管新生 / リンパ弁 / 血管新生 / FOXC / GATA / share stress / がん微小環境 / 転写ネットワーク / Foxc転写因子 / RasGAP / Foxc 転写因子 / Fox転写因子 / ゲノムワイド解析 / 遺伝子改変モデルマウス |
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| Outline of Final Research Achievements |
The lymphatic vasculature has a critical role in maintaining tissue homeostasis by returning interstitial fluid to the venous circulation, absorbing lipids from the digestive tract, and providing a network for immune surveillance and response. Mutations identified in genes involved in the VEGF-C/VEGFR3 signaling pathway are commonly associated with primary lymphedema and other lymphatic malformations, which include mutations in critical transcription factors, FOXC or GATA. FOXC1 and FOXC2 are closely related members of the forkhead box (FOX) transcription factor family. Here, we report an essential role for FOXC1 during lymphatic valve maturation and maintenance. Detailed comparison of FOXC1 and FOXC2 expression and roles in lymphatic valves suggests some overlap with a broader importance for FOXC2, but more subtle, key contribution for FOXC1.
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍組織のがん微小環境において、細胞と炎症細胞から分泌されるVEGF-C/D等のリンパ管新生因子は既存のリンパ管内皮細胞の増殖と運動を亢進し、リンパ管新生が起こる。近年VEGFC/VEGFR-3シグナルをブロックする阻害剤の臨床試験が進められているものの、リンパ管新生やリンパ弁形成を含めたリンパ管安定化を標的とした新たな治療法の開発が喫緊の課題である。特にリンパ管内皮細胞の増殖を抑制する新規因子の同定・機能解析は、腫瘍組織およびセンチネルリンパ節におけるリンパ管新生に直接関わるので、その研究成果は創薬開発に繋がる可能性を有している。
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